Mutation Query
| | | | Allele 1: | R953C | | Allele 2: | R953C | Allelic information known | | Refine query |
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| | | 953 |  |  |
| | Residue R953 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1E (residues 914-966) | | Subcluster description: | This subcluster comprises most of the fingers subdomain of the pol domain, including the O-helix and the Pol B motif (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
| Residue R953 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1E (residues 914-966) | | Subcluster description: | This subcluster comprises most of the fingers subdomain of the pol domain, including the O-helix and the Pol B motif (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
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Mutation Information
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| R953C | | | | Number of patients: (with R953C) | 4 | | Found as the only mutation: | 25% of entries (1 patient) | | Non-allelic with: | W748S (50%) R953C (25%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy, CPEO, ptosis, COX deficiency, ragged red fibers, headaches/migraines, diarrhoea, lactic acidosis, hypotonia, ataxia, myoclonic seizures, exercise intolerance, muscle weakness, muscle cramps after exercise, optic atrophy, easy fatigability. 61% mtDNA copy number in muscle, 61% mtDNA copy number in blood. | | Mutations: | R953C, W748S | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 51, Age of Death: n/a |
| Reference: | Tang et al, 2012; | | Description: | Exercise intolerance, muscle weakness, persistent diarrhea, intermittent vomiting, bilateral ptosis, cognitive impairment with poor recall and expressive language difficulty, proximal myopathy, axonal sensorimotor peripheral neuropathy | | Mutations: | R953C, W748S | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 50, Age of Death: n/a |
| Reference: | Gurgel-Giannetti et al, 2012; | | Description: | gait abnormalities and PEO, cognitive impairment and depressive and psychotic symptoms, masked face, bradykinesia, action tremor, stooped posture, rigidity, complete ophthalmoplegia, and mild proximal limb weakness, sensory polyneuropathy, myopathy, mild cardiomyopathy, Multiple mtDNA deletions in muscle | | Mutations: | R953C, R953C | | Age group: | adult | | Age of Onset: 20, Age of Patient: 35, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | PEO, ptosis, muscle weakness, hypothyreosis, ataxia, asthma, balance disturbance. | | Mutations: | R953C | | Age group: | adult | | Age of Onset: 22, Age of Patient: 29, Age of Death: n/a |
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The following information is based on existing patient data and pathogenic cluster assignment.
Pathogenicity information for a patient with mutations in Clusters 1 and 1: Age of onset information is extracted from a total of 20 patients and/ or patient families. | Age of onset | | |
20- 10- | 2
| 7
| 3
| 8
| | | infantile | childhd | juvenile | adult | | | 10% | 35% | 15% | 40% | |
All mutations mapping within the pathogenic clusters are at high risk for pathogenicity. In general, a patient must have a pathogenic mutation in both of his/ her POLG genes to develop a POLG-related syndrome. | Symptoms described in patients with cluster1-cluster1 mutations | |
| Symptoms in patients with combination
cluster1:cluster1 | | Developmental delay | 30.0% | | Movement disorder (ataxia) | 25.0% | | PEO | 25.0% | | Muscle weakness | 20.0% | | Hypotonic | 20.0% | | Dementia | 20.0% | | Status epilepticus | 15.0% | | Myopathy | 15.0% | | Ophthalmoplegia | 15.0% | | Liver failure | 15.0% | | Failure to thrive | 15.0% | | Tremor | 15.0% | | Lactic acidosis | 10.0% | | Peripheral neuropathy | 10.0% | | Ptosis | 10.0% | | Encephalopathy | 10.0% | | Vomiting | 10.0% | | Dysphagia | 10.0% | | Hepatomegaly | 10.0% | | Hearing loss | 10.0% | | No known symptoms | 5.0% | | Myoclonic seizures | 5.0% | | Hemiparesis | 5.0% | | Intractable seizure | 5.0% | | Epilepsy | 5.0% | | Cerebellar ataxia | 5.0% | | Polyneuropathy | 5.0% | | Demyelinating neuropathy | 5.0% | | Sensomotor neuropathy | 5.0% | | Exercise intolerance | 5.0% | | Parkinson's disease | 5.0% | | Jaundice | 5.0% | | Headache/ migraine | 5.0% | | Delayed gastric emptying | 5.0% | | Cortical blindness | 5.0% | | Dysarthria | 5.0% | | Respiratory deficiency | 5.0% | | Leigh syndrome | 5.0% | | Areflexia | 5.0% | | CPK abnormalities | 5.0% | | Hypoglycemia | 5.0% |
| | Data gathered from clinical descriptions for 20 patients |
| Symptoms by group | | Developmental Delay | 40.0% | | Myopathy | 35.0% | | Seizures | 35.0% | | CPEO | 30.0% | | Ataxia | 25.0% | | CNS symptoms | 25.0% | | Hepatopathy | 25.0% | | Neuropathy | 25.0% | | Other | 25.0% | | Hypotonia | 20.0% | | GI symptoms | 15.0% | | Alpers syndrome | 5.0% | | Migraines | 5.0% | | Unknown | 5.0% |
| | [Show grouping information] |
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